Abiola Julius, Berg Anna Maria, Aiyelaagbe Olapeju, Adeyi Akindele, König Simone
IZKF Core Unit Proteomics, Interdisciplinary Center for Clinical Research, University of Münster, Röntgenstr. 21, 48149 Münster, Germany.
Organic Unit, Department of Chemistry, University of Ibadan, Ibadan 200005, Nigeria.
Biomedicines. 2024 May 7;12(5):1027. doi: 10.3390/biomedicines12051027.
The vasoactive peptide bradykinin (BK) is an important member of the renin-angiotensin system. Its discovery is tightly interwoven with snake venom research, because it was first detected in plasma following the addition of viper venom. While the fact that venoms liberate BK from a serum globulin fraction is well described, its destruction by the venom has largely gone unnoticed. Here, BK was found to be cleaved by snake venom metalloproteinases in the venom of , one of the deadliest snakes, which degraded its dabsylated form (DBK) in a few minutes after Pro7 (RPPGFSP↓FR). This is a common cleavage site for several mammalian proteases such as ACE, but is not typical for matrix metalloproteinases. Residual protease activity < 5% after addition of EDTA indicated that DBK is also cleaved by serine proteases to a minor extent. Mass spectrometry-based protein analysis provided spectral proof for several peptides of zinc metalloproteinase-disintegrin-like Eoc1, disintegrin EO4A, and three serine proteases in the venom.
血管活性肽缓激肽（BK）是肾素-血管紧张素系统的重要成员。它的发现与蛇毒研究紧密相连，因为它最初是在添加蝰蛇毒后在血浆中检测到的。虽然毒液从血清球蛋白组分中释放BK这一事实已有充分描述，但其被毒液破坏的情况在很大程度上未被注意到。在此，发现BK在最致命的蛇之一的毒液中被蛇毒金属蛋白酶切割，该毒液在Pro7（RPPGFSP↓FR）后几分钟内降解其二甲基氨基苯磺酰化形式（DBK）。这是几种哺乳动物蛋白酶（如ACE）的常见切割位点，但不是基质金属蛋白酶的典型位点。添加EDTA后残余蛋白酶活性<5%表明DBK也在较小程度上被丝氨酸蛋白酶切割。基于质谱的蛋白质分析为毒液中的锌金属蛋白酶-解整合素样Eoc1、解整合素EO4A和三种丝氨酸蛋白酶的几种肽段提供了光谱证据。
